The goal of this project is the development of a vaccine for the prevention of hepatitis C viral infection. The hepatitis C virus (HCV) is the primary etiologic agent of parenterally transmitted non-A, non-B hepatitis and is a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. HCV is highly variable due to mutations within the HCV envelope proteins. These mutations lead to viral "quasi-species" that are not neutralized by the antibodies formed in response to other quasi-species. The mutations occur predominantly within the hypervariable region 1 (HVR1), found at the amino terminus of the viral envelope protein, E2. Therefore, in order for any vaccine to be effective, it must elicit antibodies capable of neutralizing any of these quasi species, and thereby prevent establishment of the initial infection. The specific aims of this phase I project are to (1) construct a multideterminant antigen, consisting of a library of known as well as potential sequences of the HVR1; (2) present this library on a highly immunogenic on carrier moiety (Advanced Antigen Presentation Platform); (3) demonstrate that this construct binds anti-HCV antibodies; and (4) demonstrate that this immunogen induces high titre anti-HCV envelope antibodies. Phase II studies would involve assessing the protective efficacy of such an immunogen in susceptible hosts. PROPOSED COMMERCIAL APPLICATIONS: Over 300 million people are infected with HCV. Elimination of this disease will require a vaccine. Based on the hepatitis B virus this would represent about a $500 million dollar per year product.